Andrew Bryant, MD

Division of Pulmonary and Critical Care MedicineVanderbilt University School of MedicineTitle: "Role of Hypoxia-Inducible Factor in the Development of Secondary Pulmonary Hypertension"Term: January 15, 2013 through January 14, 2014

Summary of Research Project:

Development of secondary pulmonary hypertension in the setting of idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with worsening symptoms of dyspnea, quality of life, and poorer prognosis. Hypoxic-inducible factor (HIF) is a primordial regulator of the cellular response to lack of oxygen. Our research project evaluates the role of HIF in the development of secondary pulmonary hypertension utilizing a mouse model with specific deletion of HIF in vascular endothelial cells. We hypothesize that upon development of experimentally induced lung fibrosis, mice without expression of HIF within the vascular endothelium will be protected against the development of pulmonary hypertension. Furthermore, we hope to demonstrate decreased right ventricular remodeling in these mice under chronic hypoxic conditions, providing another mechanism of protection that bears further evaluation.

There are currently few available disease-modifying therapies to offer patients with COPD and IPF, with the exception of tobacco cessation and lung transplantation, which itself carries a limited long-term prognosis. Efforts to treat pulmonary hypertension in patient populations of both COPD and IPF, mainly with oral phosphodiesterase inhibitor sildenafil, have proven unsuccessful. Thus, there is a serious need for alternatively acting agents to help these patients. Our studies indicate novel pathways that are active in the development and sustainment of pulmonary vascular disease pathology, specifically activation of conserved responses to local and global hypoxia – the hypoxia-inducible factor (HIF) pathway. With further study, it is our hope to uncover more details of this pathway, allowing downstream targets to be discovered that may be amenable to pharmaceutical treatment.

T32 HL086638 (Bernard), 04/01/2007–06/30/2014NIH/NHLBI“Clinical and Translational Research Training Program in Pulmonary Medicine”Role: Postdoctoral FellowThis training grant is designed to train and mentor researchers in all aspects of clinical and translational research necessary to prepare them for the unique challenges associated with advancing science in Pulmonary and Critical Care Medicine. Dr. Bryant started on the training grant on July 1, 2012.

Departmental Funds (Blackwell/Lawson), 07/01/11-present“The Role of Hypoxia-inducible Factor in the Development of Pulmonary Hypertension and Lung Fibrosis”Role: Research FellowIn this study we are using multiple mouse models to characterize hypoxia-inducible factor (HIF) in lung fibrosis and pulmonary hypertension. From these investigations, we will gain better understanding of the role, regulation and downstream mechanisms of chronic lung hypoxic responses.

Research Grant (Bryant), 01/15/13–01/14/14American Thoracic Society $50,000“Hypoxia Inducible Factor Regulation of Secondary Pulmonary Hypertension”Role: Principal InvestigatorIn this study we are using a mouse model of pulmonary fibrosis to characterize hypoxia-inducible factor (HIF) in development of secondary pulmonary hypertension. We plan to gain understanding of the role of hypoxic signaling in response to chronic lung disease, specifically pulmonary fibrosis.

There is no scientific or budgetary overlap among active or pending research grants.

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